Date of Award

2013

Degree Type

Thesis

Degree Name

Master of Science

School

School of Medical Sciences

Faculty

Health, Engineering and Science

First Advisor

Dr Peter Roberts

Second Advisor

Dr Phillip Matson

Abstract

Molecular biomarkers are chemical signatures that all cell types possess. They are used in medicine to evaluate both normal biological events and pathogenic processes. A series of biomarkers associated with cancer of the breast, ovaries and other parts of the female reproductive tract and the monitoring of pregnancy were measured in disease‐free women. The biomarkers measured were prostate specific antigen (PSA), CA125, CA15‐3, CA72‐4, and pregnancy associated plasma protein‐a (PAPP‐A). The patterns of change during natural and stimulated ovarian cycles and early pregnancy were investigated to determine if these biomarkers could reflect normal events relating to ovulation and implantation/placentation. In addition, the study was able to investigate the possible erroneous crossing of clinical cut‐off values associated with disease due to other biological processes rather than the disease itself.

total of 73 blood samples (10 women) taken throughout the natural menstrual cycle, 64 blood samples (11 women) during stimulated ovarian cycles and 86 blood samples (14 women) during early pregnancy monitoring were collected and all samples were analysed by batch analysis on the Roche Cobas e411. Concentrations of CA125, tPSA, CA15‐3 and CA72‐4 showed no significant difference between the natural and stimulated ovarian cycle groups (p≥0.5989). On average the mean PAPP‐A of the natural group was 2.41±0.58 mIU/L higher than the stimulated group (t = 4.10, p < 0.001). CA125 and CA15‐3 results were both significantly influenced by the stage of the cycle (p=

In conclusion, batch analysis of all samples from each of the participants was conducted to maximise the possibility that any changes seen in biomarker concentrations were due to biological fluctuations and not because of assay variability. Ovarian stimulation reduced serum PAPP‐A levels, whilst CA125 and CA15‐3 were unaffected by ovarian stimulation per se but showed cyclical changes throughout both natural and stimulated cycles. PAPP‐A, CA125, tPSA and CA15‐3 all showed consistent changes in early pregnancy, and their combined benefits as markers of different aspects of implantation, embryogenesis and placentation warrants further investigation. Only CA125 in early pregnancy crossed the cut‐off associated with disease, ie ovarian cancer, and other gynaecological and inflammatory conditions. Care must therefore be taken when using CA125 determinations to detect disease if the woman is less than 7 weeks pregnant as transient elevations during this time appear normal.

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